Gynaecology

Hananja Brice-Ytsma MNIMH, MSc

Hormones

Hormones are all of steroid formation, the central part being cholesterol, and are structurally similar to cholesterol. Each hormone has minor changes which gives it characteristic effects within the body.

Ovarian secreted hormones

oestrogen

progesteron androgen

inhibin

Oestrogen; source

Ovaries secrete oestrogen in the active form; oestradiol, of which some get converted to oestrone, the weaker form.

• Both go into the blood stream, and stimulate cell growth, the oestrogen levels peak just before ovulation, and remains elevated during the second half of cycle. Levels drop before the menstruation.

Oestrogen sourceSecond source is the conversion from

androgens to oestrone (the weaker oestrogen) by the aromatase enzyme.

Aromatisation occurs in the hair follicles, skin, brain, bone, bone marrow, muscle (25%) and fatty tissue (10-15%), (this is where Paeony and Glycyrrhiza play a role).

post menopausal women derive almost all their oestrogen (oestrone) from the aromatisation of androgen in fatty tissue, and muscle.

Oestrogen source

Before menopause most of the oestrogen is produced by the ovaries, and small percentage by aromatisation of androgens

to oestrogen. • Thin women may be deprived of this secondary

source, and may develop menopausal symptoms.

• Oestradiol is converted to

– 2-hydroxyoestrone (good and protective) and to

– 16 hydroxyoestrone ( which has been shown to increase in the presence of chemical contaminants, such as environmental oestrogens)

– Oestrogen enter the liver and get conjugated;

» where they get deposited with the bile into the gallbladder and excreted in the faeces (tar.rad)

» In the colon they can be acted on by beta-glucuronidase (which is provided by the intestinal bacteria); deconjugated.

» excreted

» or reabsorbed back into the blood stream.

The role of Oestrogen Potentiate growth of nerves and nerve cells increased blood flow to the brain, aiding brains use of glucose, reduces the negative effects of stress, prevention formation of free radical nerve toxins, (lack

of sleep leads to free radical damage).

The role of oestrogen (cont.)• give maintenance to the structure of skin, blood

vessels, bone strength, stimulates proliferation where there are oestrogen receptors

• thickening, elasticate, lubricate tissue in the vagina and vulva

• hormonal and growth enhancing effects, responsible for body fat around the abdomen , hip and breasts, stimulates the growth of uterine muscle and endometrium,

The role of oestrogen (cont.)

• reduced oestrogen as in the menopause leads to vulva losing collagen, fat and water retaining ability

• so flattens, thin, dry and looses tone.

• Vagina shortens, narrows, the wall of vagina thinners, less elastic and pale in colour,

• leading to vaginal dryness, vaginal discharge and dysparunia, this also happens in the other tissue.

The role of oestrogen (cont.)• initiates an increase of number of receptors on each

cell, so more cells are produced in oestrogen rich environment, which leads to escalating ability of oestrogen to stimulate cell growth and increase the number of places for oestrogen to interaction

• The circulating oestrogen can go to the kidneys, and changed into

– oestrone which is very weak, about 80% less potent than oestradiol, so is much like the plant hormone, these form the base of some pregnancy test and is used to tell the health to the placenta.

Oestrogen and temperature regulation Oestrogen levels lower in premenopausal women

with hot flushes than those without. Post menopausal low estrogen levels, puberty low oestrogen but no hot flushes, during pregnancy hot flushes can be present when oestrogen very high.

Oestrogen plays a role in the temperature regulation, some suggest it is imbalance in the beta-endorphins and other opiates in the brain which may influence temperature regulation, cause withdrawal of opioids and trigger hot flush (possibly the place where Cimicifuga plays a role).

Oestrogen deficiency

Effect on Memory and cognition; specific cognitive changes that occur when oestrogen is rapidly withdrawn from the system. most commonly short term, memory loss. It is seen most dramatic after childbirth or after

oophorectomy. This is worsened by difficulty sleeping.

Oestrogen deficiency

Depression; women who take oestrogen alone, were best mood wise, adding progestin reduced the mood elevating effects of oestrogen (perhaps one of the reasons Vitex not always useful when depression related with PMS).

Oestrogen metabolism interference

Body weight 15-20% below ideal can cause menstruation to stop and oestrogen below normal will lead to erratic cycle, reduce fertility and reduced bone density, and vaginal dryness.

Excess fibre leads to lower levels oestrogen. Vitamin A deficiency, leads to decreased activity

of 3 beta-dehydrogenase vital for the production of oestradiol in ovary.

Oestrogen metabolism interference

• Antibiotics leads to reduced bacteria to convert oestrogen to re-enter the circulation, plus phytoestrogens are bioavailable in the presence of healthy bacteria

• Over exercising leads to the reduction of circulating oestrogens; amennorhea and low bone density.

• Smoking alter metabolism so more of the inactive oestrogen is produced and leads to a earlier menopause and increased incidence of osteoporosis.

Phytoestrogens and environment oestrogens

• fit on the receptor sides of the oestrogens.• Environmental oestrogens accumulate in fatty tissue, and tends to be high in

the those who consume lots of meat. • found in plastics, eg food raps around high fat containing foods. Breathing air,

burning rubbish, the water.• Pesticides. • Levels of DDT were found to be higher in fibroid tissue then in normal tissue,

prenatal exposure may alter sexual maturation of foetus, esp. males, and influence fertility.

– Singly little effect, the combination exerted effects are 1000X more potent than any one chemical alone.

– With endogenous oestrogen the body is only affected during the years of sexual maturity, with the environmental oestrogens one is exposed from the foetus years and on, and accumulates over the years.

Excess oestrogen; symptomsHeavier than usual

menstruation.Longer than usual

menstruationPMTMenorrhagia, endometriosis,

fibroids, fibrocystic breast disease, breast and endometrial cancer.

Excess oestrogen

Levels high comparative and not detected in single blood test.

Length of time of over exposure (time when period started, number of pregnancies, breast feeding, menopause).

Menarche; the age of the menopause has not changed, it is a fixed biochemical/ physical time. However menarche has, in 1840 the average age was 16.5, in 1990 the average age is 12.8. Mean weight is about 47.8kg.

In a lifetime; being exposed to more periods than our ancestors.

Excess oestrogen; causes

Over exposure to oestrogen; due to lifestyle, impaired excretion via liver and bowel.

Exposed to higher levels of environmental oestrogen.

Saturated animal fats encourages the growth of particular intestinal bacteria, which produce, enzyme beta-glucuronidase: high fat intake is related to benign breast disease, Ca, heavy menstruation, endometriosis, and fibroids.

Relative excess, i.e. lack of progesteron (anovulatory cycle as in perimenopause, puberty).

Causes excess oestrogen (cont.)

• A diet in excess of refined carbohydrates, low fibre, high saturated fats, leads to increase of oestrogen dependent complaints (epidemiological studies).

• Obesity; interferes with the ovarian function, and is linked with increased levels of oestrogen, more conversion of androgens to oestrogen.

• high upper body fat, is related to reduced levels of SHBG, which lead to the presence of more free oestrogen.

• Fibre reduces oestrogen levels in blood and urine, probably via influencing intestinal bacteria, vegetarian have lower enzyme activity.

Causes excess oestrogen (cont.)• B6 Deficiency; leading to an increased susceptibility of

the tissues in the uterus and breast to the effects of oestrogen.

• B6 deficit breast cancer patient has a poorer survival rate.

• The liver uses various B vitamins to detoxify oestrogen and excrete it in the bile.

• Alcohol interference; moderate consumption leads to reduced oestrogen, and reduced incidence of uterine cancer especially in overweight women, but increases breast cancer.

Treatment of oestrogen excess• Lactobacillus acidophilus; reduces activity of beta glucuronidase; research has shown

that eating these products reduces the incidence of cancer, possibly due to affecting the reabsorption of oestrogen and or other immune enhancing effects of the bacteria.

• Phytoestrogen; competitive inhibition• Slow down the conversion of androgen to oestrogen (weight loss). • make oestrogen relative unavailable by increasing levels of SHBG (exercise and look at

thyroid).• Protein improves the metabolism of the liver,

• Cabbage rich in indoles; increases the liver changes of oestrogen to water soluble form, and get excreted via faeces.

• Indoles competitively inhibit oestrogen in vitro, inhibit growth of breast cancer cells, e.g. Capsella.

Capsella bursa pastoris

Member of the cabbage family. In vitro test; shown to accelerate coagulation of the

blood, however in vivo no haemostatic properties found (1969)

Diuretic, anti-inflammatory, anti ulcer, oxytocic and anti-haemorrhagic, tumour inhibiting, antimicrobial effects.

Used for menorrhage.cooling and drying.4-6ml of a 1:2 per day.

Excess oestrogen and liverCholestasis, i.e. diminished bile flow, and stasis

of bile (e.g. seen frequently in pregnancy and OCP users, and high incidence of gallstones ).

Liver herbs; increase bile flow, increase clearance of cholesterol and oestrogen, alter bowel flora (Taraxacum off. Radix).

Use cholagogues and choleretics such as Taraxacum officinalis radix, Carduus marianus, Berberis vulgaris, Rumex crispus.

Oestrogen excessFoods high in methionine assist with the

methylation of oestradiol and estriol, found in legumes, onions, and garlic.

Exercise helps with oestrogen clearance, women will have lighter and less frequent periods (increases SHBG, increases cell sensitivity to insulin, which affects hormones).

Phytoestrogens

Isoflavones; genistein, daidzein, and their glycosides mainly found in the Leguminosae such as soy and red clover.

Lignans; flaxseed contain lignans enterodiol, and enterolactone, formed by bacterial action on the precursor secoisolaricresinol diglucosides.

Glycine max

Soya bean

Constituents;

35% proteins20% lipids30% carbohydrates9% fibreVitamins and mineralsIsoflavones; genistein, daidzeins, glycitein and their glucosides genistin, daidzin, glycitin, and a small amount of coumestrol.

Pharmacodynamics

- The isoflavonoids are inactive when present in the bound form as glycosides.- The glycosides undergo fermentation by the intestinal flora.- Urinary recovery can vary from 15-66% for the isoflavones. - Urinary recovery greater for fermented soy products, than unfermented. - Presence of fibre correlated positively with urinary excretion of isoflavones. - Individual variability in colonic micro flora.

-

Epidemiology

Japan, China and Korea; Lower incidence of most common cancers in the western world.

Hormonal activity

- RCT shown that soy rich diet can have an effect on hot flushes.- Overall little effect found on serum LH, FSH, with the exception of one trial showing increase in SHBG.- Little or no impact on the genital tract, endometrium or vagina.

Phytoserms; (phyto selective estrogen receptor

modulator) 2 estrogen receptors identified; alpha and beta.

ERAlpha; - leads to uterine proliferationERBeta;

- expression in the breast is low- most strongly expressed in the ovary,

prostate, bladder, lung. - expressed preferentially in normal breast and ovarian tissue. - abundantly in granulosa cells in early stages of follicular development, so could inhibit oestradiol

ERAlpha

Preferentially expressed in ovarian cancer lines, and Estrogen receptor node-positive breast cancers.

Genistein; has significantly higher affinity for ERBeta than for ERAlpha.

Coumestrol; binds as strongly as 17Beta-estradiol to both human estrogen receptors.

5-Omegenistein, formononetin; Significant binding to Alpha

Antitumour activity

Genistein; inhibition of angiogenesis, inhibition of tumour

invasiveness, inhibition of cell cycle progressing, inhibition of enzymes in oestrogen biosynthesis, antioxidant effect, tyrosine kinase inhibitor.

Antiproliferative effects achieved with low dose isoflavone treatments, using

soy preparations rather then purified compounds.

Biphasic effects;

Low dose genistein inhibitory effects, high doses increased growth.

Phytoestrogens are weak estrogens and under certain experimental conditions will stimulate proliferation and estrogen-dependent gene-expression.

Prevention of cancer

Japanese breast cancer and prostate cancer patients better survival than others.

Gastric cancer with high tofu consumption better outcome.

HRT breast cancer better survival than those not on HRT before; tumours tend to be smaller and better differentiated.

Prevention of cancer

Single pregnancy, timing of pregnancy. During pregnancy hormones, provoke proportion of non differentiated epithelial cell of breast to undergo differentiation to milk producing cells, reducing epithelial cells the targets of carcinogens.

Aptosis after pregnancy; elimination of the epithelial cells that have undergone mutation.

Increased risk with earlier menses and later age at menopause.

Increased risk with higher bone mineral density, and obesity.

Prevention of cancer

Animal data; genistein lead to higher proportion of the epithelial cells of breast to be differentiated so therefore reduce breast cancer risk.

Animal data; tamoxifen and soy reduced carcinogenesis double in combination as suppose by tamoxifen alone.

Prevention of cancer

Early exposure to soy shown there is lower incidence of breast cancer.

Question; does taking soy later in life have a protective affect, or make a difference when breast cancer present?

Other effects of soyaSoya decreased serum concentration total cholesterol, LDL cholesterol, triglycerides, HDL increased nonsignificantly (47.gr soy a day). Inhibiting cell adhesions, alter growth factor activity and inhibit cell proliferation involved in atherogenic lesions formation.

Retention of bone mass, hip fracture in Hong Kong one-third the rates of US.

Bone density

Bone mineral density and bone mineral content (BMC) of lumbar vertebrae gain found, no increase in proximal femur bone mass.

Oestrogen receptor Beta expression higher in osteoblastic cell line.

Conclusion

Consumption of soya and plant based foods is consistent with recommendation to increase fibre, antioxidant intake, while lowering sources of saturated fat.

Questionable; supplementation with isoflavonoids

Trifolium repens

Red clover

Constituents- Isoflavones in the leaves; biochanin A, genistein, daidzein (the isoflavone composition of soy and red clover are different).- Formononetin in the flower heads.

Red clover has a much higher theoretical oestrogenicity compared to soya products.In soy the isoflavonoids are mainly bound as betaglycosides, acetyl beta-glycosides and malonyl beta glycosides, while in red clover they are present as malonyl glycosides..

History

Red clover became of interest when in the 1940s, Australian sheep grazing large quantities, developed extensive lesions on the reproductive organs, developing cystic endometrial hyperplasia.

Traditional use

Dermatological conditions, syphilis, glandular conditions.Topically used for growths, swellings and cancers eg breast cancer.Since the 1940s included in the Hoxley anti-cancer formula, which is still used in some cancer clinics.

Clinical trials;

Clinical trials done with the isoflavones of Red Clover.The results vary, some promising and one showing some promise with bone density.Research with trifolium is usually interpreted together with soy isoflavones, and a distinction is not always made.

Steroidal saponins

Saponins; increase FSH levels in women by binding with, and weakly stimulating, hypothalamus oestrogen receptors, this leads the body to think that oestrogen levels are lower (because they are weakly oestrogenic), which leads to increase levels of oestradiol production.

Herbs containing steroidal saponins

Dioscorea villosaChaemelerium luteumTribulus terrestis

Dioscorea villosa

Constituents; steroidal saponins dioscin, diosgenin, the aglycone of dioscin was used industrially to produce progesterone and cortisone.

Actions;

SpasmolyticAnti-inflammatoryAntirheumaticOestrogenicHypocholesterolaemic

Historical use;

Eclectics; favourite remedy used for spasmolytic activityAmerican Indians; colic, relieve of pain in childbirth

Pharmacology;

Possibly oestrogenic effect by binding with oestrogen receptors of the hypothalamus, which are part of the negative feedback mechanism of oestrogen control.In premenopausal women interaction of these compounds with receptors in the hypothalamus or pituitary displaces oestrogen from the receptors and blocks oestrogen feedback.

Because the oestrogenic substances are very weak compared to the normal oestrogen; The body thinks that the oestrogen levels are lower what they really are and respond by increasing FSH, hence oestrogen production increases.

Peri- and postmenopause; possible mode of action.

Low oestrogen environment; the steroidal compounds bind to vacant receptors in the hypothalamus, the selective binding reduces the symptoms of hot flushes by convincing the body that there is more oestrogen present in the bloodstream than there actually is.

In post menopausal women they may interact with secondary oestrogen receptors, such as in the hypothalamus, to decrease the symptoms of oestrogen withdrawal.

The sapogenins or their metabolites may potentiate the activity of endogenous oestrogen on both primary and secondary receptors.

In the postmenopausal women sapogenin may directly or indirectly via hypothalamus and/or pituitary gland increase the production of oestrogen precursors from the adrenal cortex,

In the premenopausal women sapogenins (diosgenin) and their metabolites (dioscin) may interact with receptors in the hypothalamus or pituitary to increase FSH and so increase oestrogen production.

Has no progesteronic effect.

Research from sapogenins in tribestan.

Females; LH, and testosterone slighly increased. FSH, oestradiol increased.

Males; LH, testosterone, oestradiol increased FSH no increase.

Diosgenin effect on cholesterol metabolism;

Interferes with absorption of dietary and endogenous cholesterol..Enhanced cholesterol secretion into bile.

End result leads to;1. Increase in excretion of cholesterol without effecting excretion of bile acids.

2. Reduces the acute cholestatic effect induced by oestradiol,

3. Reduces internal inflammation and normalised bile secretion in an experimental model

Clinical trial;

Reduced serum lipid peroxidation and serum Triclycerides.Increased HDL cholesterol levels.No changes in total cholesterol or LDL cholesterol.

Pharmacokinetics;

Glycosides such as dioscin are broken down in the large intestine by microbial activity to form the aglucone diosgenin.Need a healthy gut flora.

Chamaelerium luteum

False Unicorn

Old eclectic remedy

Main effect on reproductive organs.Typical picture; fullness, heaviness, congestion in the pelvic area, it feels as if everything is going to drop out. Lumbar pains, down the thighs, and back of legs, restlessness and general weakness.To overcome excessive fatigue.

William Cook 19th C physiomedicalist

‘It scarcely has an equal in atonic forms of prolapse, leucorrhea, passive haemorrhage, menorrhagea, and similar enfeebled conditions. While its use in sensitive patients and irritable uterine conditions is to be avoided, it can be used to the greatest advantage in flaccid and prostated states for the maladies above named. Also to be used in general depression of the vital force.’

Substitute; Aletris farinosa

Commonly substituted but historical medical literature weighs in strongly against it. Substitution continued till the 1920’s, Felter and Cook felt any therapeutic reputation was due to the adulteration with Chamaelerium.

Actions and indications

To tone up the female reproductive organs, improving their function and nutrition. Pelvic warming. Strengthens the uterus; preventing miscarriages and tendency to abort.Dysmenorrhoea; with bearing down feeling. Leucorrhoea, amenorrhoea.Antiemetic and antinausea; in pregnancy.General tonic; anorexia, dyspepsia of the atonic type Diuretic; strangury, acute and chronic nephritis especially if patient depressed. Bitter, Jaundice.Some cases of rheumatism, however other more effective remedies are around.

Constituents;

Steroidal saponins; Chamelirin, which is a glycoside of diosgenin,

Pharmacology;

Amphoteric effect on hormonal secretion by the ovary, however Chamaelerium has never been subjected to the lab. Speculation that the effect is as the steroidal saponins in Dioscorea.

Comparison

Chamaelerium Trillium Dioscorea

1:3 contains0.3% steroidalsaponins

1;3 contains1.2 % steroidalsaponins

1:3 contains3% steroidalsaponins

Cimicifuga racemosa

Black cohosh

Frequency of use

In 1997 over ten million monthly units of Cimicifuga racemosa extract was sold in Germany, United States and Australia.Plenty of trials done, but could be interpreted as biased since most done by the manufacturer of Remifemin.

Constituents

Triterpene glycosides xylosides, actein, cimicfugoside, 27-deoxyactein.Isoflavone formonetin, however is more concentrated in aerial parts of the plant.Isoferulic and salicylic acids.

Importance of the whole plant

Efficacy of methanolic extracts of the root is dependent upon at least three different fraction with a synergistic action.

Europe

In use since the 17thC for problems of the female reproductive organs

History, used by American Indians

Tonicrheumatism a decoction of the root was used as a footbath, and steamed sweat bath.analgesic for different kinds of pain such as dysmennorrhoea, childbirthdiuretic, emmenagoguefresh poultices for snake biteused for malaria

Eclectics

An alcohol extract was adopted by the eclecticsUsed widely by the american physicians over the 18-19thC for different gynaecological conditions.

Dr.John King

Acute and chronic cases of rheumatism, inflammatory conditions, pulmonary afflictions, neuralgic afflictions.King felt it was especially efficacious in maladies of the female reproductive organs chronic ovaritis, endometritis, menstrual derangement, amenorrhoea, dysmenorrhoea, menorrhagia, frigidity, sterility, threatened abortion, uterine subinvolution,

Actions

Astringent, diuretic, diaphoretic, antirheumatic, antitussive, antispasmodic, aphrodisiac, emmenagogue, nervine, sedative, stomachic, traditionally and still used today to stimulate labour.

Recent history

Since the mid 1950s widely used by German gyneacologists by 1962 there are 14 clinical studies involving 1500 patients, for perimenopausal symtoms

Since the 1950s used more for gynaecological indications; intermittent bleeding, disturbances in the menstrual cycle, PMS as well as climacteric complaints. Especially hot flushes and psychic complaints.

Pharmacology

Effect noted in the hypothalamus to reduce serum LH levels, effects on bone to prevent osteoporosis, oestrogenic effect in the urinary bladder, and no uterotrophic effects seen.This led to speculation that CR is an ideal Selective Estrogen Receptor Modulator.

A compound that in contrast to pure estrogen agonists or antagonist, have a mixed and selective pattern of estrogen agonists-antagonist activity, which largely depends on the tissue targeted.

1944 Gizycki profided first evidence of estrogenic effects.Oestrogenicity was measured by effect on the uterus, with the understanding of ERBeta could explain the contradictory results in the past if CR was estrogenic or not.However CR was found not to bind to ERAlpha or ERBeta.Presence of Ergamma????

Other suggestions on mode of action

Dopaminergic activity which could explain the reduction of hot flushes, and by lowering prolactin levels have an effect on bone loss (High prolactin levels have been associated with premature loss of bone due to concomitant hypogonadism). This would give it similar actions as the vitex agnus castus.Dopaminergic agonist also cause decrease in proliferation of MCF-7 cells.

Inhibitory effect on the hypothalamus.Effect on neurotransmitters, serotonin receptor

blocking activity. Jarry et al 2003 in vitro tests were able to separate

the dopaminergic compounds and to distinguish between dopaminergic and estrogenic activity. Both are contributing to the overall pharmacological profile. Inhibitory effects on the pituitary LH secretions, so mimicking the negative feedback effects of estradiol within the hypothalamus.

Antiproliferative action of CRCR does not bind to the known estrogen alpha or beta receptors, so the anti-tumour activity may be mediated via another mechanism..

Inhibitory action of CR on proliferation of the ER Alpha MCF7 cells.

CR inhibited estradiol induced MCF-7 cell growth.

Aryl hydrocarbon receptor (AhR) activation explains why CR has also antiproliferative action of ER negative breast cancer cells (T47D), AhR is widely expressed in mammalian tissue and tumours.

CR compounds potently inhibit growth of human prostate cells in vitro, which may be mediated via the AhR. Aryl hydrocarbon receptors activation leads to inhibition of growth of tumours

Dopaminergic antiproliferative action. Or it may be speculated that CR constituents address a yet

unknow third subtype of ER

CR with tamoxifen

When tamoxifen was added to the CR treated estrogen sensitive breast cancer cell line, a greated inhibition in cell growth was seen than in tamoxifen alone.Clinical trials showed that a combination therapy of tamoxifen and CR helped with reduction of hot flushes, and improved quality of life.

Effect on bone

Clinical trial (Wutke 2003) showed that CR and conjugated estrogen have comparable effects on serum markers of bone metabolism, and thus have osteoprotective effects.

Effects on bone metabolism

Decreased activity of the osteoclast cells, responsible for bone degradation.The bone specific alkaline phosphatase, the marker for bone formation, increased under CR (remained unchanged under (CE), indicating increased activity of the osteoblast cells responsible for bone formation.

Recent trials

Indicated CR is effective for patients suffering from moderate symptoms as supposed to mild symptoms.Supported by another trial indicating that CR is effective in relieving early climacteric symptoms.Statistically significant improvement of bonemetabolism seen with CR.

Effect on the endometrium and vagina

No change with CR on the endometrium, unlikely that CR will stimulate the uterus to develop uterine cancer. So where as progesteron is added to HRT to prevent uterine cancer, not needed with CR.Increase on amount of superficial cells in vaginal smear seen with CR, which will lead to lowering pH. Lower pH will lead to preventing ascending infection.Increase lubrication upon sexual activity.

Other effects

Favourable effect on hepatic and lipid metabolism, leading to prevention of atherosclerosis.Oestrodial can reduce weight, by having an effect on leptin, a hormone produced by the fat cells, feeds back into the hypothalamic satiety centre, to reduce food intake. CR on rats shown the same effect.

Effects on urinary bladder

Changes of tone, increased muscle tone was measured in the bladder (animal studies)possibility of effect on urinary incontinence.

Trials on breast cancer patients

One trial indicating lower of the most debilitating symptoms of sweating. (short trial of only 2 months and some were using tamoxifen, and many older women in the trial.)Another trial where CR used for over 12 months, pt younger and more severe symtoms showed significant reduction.

Dosage

One clinical trial compared 40mg CR vs 127 mg per day, similar results in safety and efficacy was observed in both dosages. Current recommendation is based on this trial, however most the dosage used in most clinical trials have been 80mg

Side effects

GIT disturbances.Dizziness, headache, weight gain.Overdose; nausea, vomiting, vertigo, headache, hypotension, impaired vision, impaired circulation.One case reported of autoimmune hepatitis (however was taking other medication).

Conclusion

Effective especially in perimenopausal women with more severe symptomsLooks promising on the effect of bone metabolism and may have a role to play in osteoporosis.Helpful in menopausal symptoms in breastcancer patients.Not stimulating uterine growth.

perimenopausal Hormonal; Oestrogenic herbs (Dioscorea, Trillium, Trifolium), soyfoods,

linseed, legumes, nuts.(make sure healthy gut flora), Glycyrrhiza glabra. Adrenal support such as the adaptogens, e.g. Panax, or Eleutherococcus,

Cimicifuga racemosa, Astragalus, Salvia. Sweating; Salvia, Astragalus. Nervine; Hypericum, Verbena officinalis (cooling), Avena sativa. Circulatory herbs; Angelica sinensis (this is not an oestrogen herb),

Ginkgo, Achillea millefolium. Digestive, assimilation, gut flora; Verbena officinalis, Berberis vulgaris,

Taracacum officinalis, radix, Artemisia absinthum (bitters are cooling) Elimination; Tarax rad., Carduus marianus, Schisandra.

Eleutherococcus senticosis

Normalise the hypthalamic-pituitary-adrenal function.

Study; improve symptoms of fatigue, insomnia, and depression in women with menopausal symptoms.

Some oestrogenic properties

Glycyrrhiza glabra

Oestrogenic (beta-sterol, formononetin, courmarin, and other flavonoids).

Encourages aromatase activiey, so increase transversion of androgens to oestrogens

Case history62 year woman presenting with severe hot

flushes since her GP advised her to go of HRT, due to breast cancer in her family history. She had gone on HRT because she had severe hot flushes, about 12 a day and 6 in the night, and the HRT had helped.

She had tried some black cohosh from the health food shop, but no effect.

Worse when on the phone and at work, none when on holiday.

Also had vulvodynia, especially before going on holiday, for which the GP prescribed Amitriptyline (Elavil) (is a psychoactive drug and pharmaceutical of the tricyclic antidepressant) which did help.

Stresses at home, had to look after her elderly mum.

On systemic enquiry, has IBS like symptoms, and is careful with her diet, and tends to be a worrier.

Some aching joints present, worse on use.